Fetal water diseases, which include hydrops fetalis and polyhydramnios, are an increasingly common cause of infant mortality and morbidity. Nearly all fetuses with the non-immune form do not survive. Yet the mechanisms that underlie the pathophysiology are unknown. This application is based on the umbrella hypothesis that a number of primary fetal abnormalities cause fetal water diseases through a common pathway-alterations in the physicochemical properties of the placental barrier. The application is designed to quantitate missing pieces of data that will allow us to estimate the physical forces that regulate the movement of water across the placenta in normal and diseased patients. Aim l of the study is to measure the diffusion permeability of the tracer substances of different molecular weights and charges in normal placentas from pregnancies with water disease. Aim 2 is to estimate the hydraulic conductivity and reflection coefficients of several important molecular species from the in vitro perfused placentas of hydropic and polyhydramniotic patients and from normal control patients. The data for these two specific aims will provide the basis for predicting the roles of disturbances in the forces that drive water across the placenta under normal and pathological conditions.